Interleukin-10 receptor, Interleukin-35 receptor, and Transforming growth factor-beta receptor (IL10R/IL35R/TGFBR)

The target group consisting of receptors for Interleukin-10 (IL-10), Interleukin-35 (IL-35), and Transforming Growth Factor-beta (TGF-beta) represents a critical axis of immune regulation on effector cells. The IL-10 receptor (IL-10R), composed of IL-10RA and IL-10RB subunits, signals via the JAK1/STAT3 pathway to exert potent anti-inflammatory effects by inhibiting the synthesis of pro-inflammatory cytokines (Moore et al., 2001, Annual Review of Immunology). The IL-35 receptor (IL-35R) is a unique heterodimer (typically IL-12RB2 and GP130, or IL-12RB2 and IL-27RA) that mediates the suppressive functions of IL-35, a cytokine primarily produced by regulatory T cells to inhibit effector T cell proliferation (Collison et al., 2007, Nature; Wang et al., 2014, Nature Medicine). The TGF-beta receptor (TGFBR) complex, involving TGFBR1 and TGFBR2, acts as a serine/threonine kinase that triggers SMAD-dependent signaling to suppress immune cell activation and promote tissue remodeling (Massague, 2012, Nature Reviews Molecular Cell Biology). These receptors are frequently overexpressed or hyper-activated in the tumor microenvironment, facilitating immune evasion by inhibiting the activity of cytotoxic T lymphocytes and natural killer cells (Vignali et al., 2008, Nature Reviews Immunology). Consequently, they are major targets in oncology for checkpoint inhibition (e.g., TGF-beta traps like Bintrafusp alfa) and in inflammatory diseases for immune restoration (e.g., IL-10 agonists like Ilodecakin) (Batlle & Massague, 2019, Immunity).

Other names

Immunosuppressive cytokine receptorsRegulatory cytokine receptorsIL-10/IL-35/TGF-beta receptor axisAnti-inflammatory cytokine receptors

TGF-beta receptor inhibition, IL-10 receptor activation, SMAD signaling modulation, STAT3 signaling induction.